4C2Z

Human N-myristoyltransferase (NMT1) with Myristoyl-CoA and inhibitor bound

4C2Z の概要

• エントリーDOI: 10.2210/pdb4c2z/pdb
• 関連するPDBエントリー: 4C2X 4C2Y
• 分子名称: GLYCYLPEPTIDE N-TETRADECANOYLTRANSFERASE 1, TETRADECANOYL-COA, 2,6-dichloro-4-(2-piperazin-1-ylpyridin-4-yl)-N-(1,3,5-trimethyl-1H-pyrazol-4-yl)benzenesulfonamide, ... (8 entities in total)
• 機能のキーワード: transferase, myristoylation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: P30419
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 99242.86

構造登録者

Thinon, E.,Serwa, R.A.,Brannigan, J.A.,Brassat, U.,Wright, M.H.,Heal, W.P.,Wilkinson, A.J.,Mann, D.J.,Tate, E.W. (登録日: 2013-08-20, 公開日: 2014-10-01, 最終更新日: 2024-05-08)

主引用文献

Thinon, E.,Serwa, R.A.,Broncel, M.,Brannigan, J.A.,Brassat, U.,Wright, M.H.,Heal, W.P.,Wilkinson, A.J.,Mann, D.J.,Tate, E.W.
Chemical Proteomics Defines the Mammalian N- Myristoylated Proteome in Live Cells Global Profiling of Co- and Post-Translationally N-Myristoylated Proteomes in Human Cells.
Nat.Commun., 5:4919-, 2014

PubMed Abstract: Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells.

PubMed: 25255805
DOI: 10.1038/NCOMMS5919

実験手法

X-RAY DIFFRACTION (2.08 Å)